Mink van der Molen DR, Batenburg MCT, Maarse W, van den Bongard DHJG, Doeksen A, de Lange MY, van der Pol CC, Evers DJ, Lansdorp CA, van der Laan J, van de Ven PM, van der Leij F, Verkooijen HM, et al.
JAMA oncology. Date of publication 2024 Apr 1;volume 10(4):464-474.
1. JAMA Oncol. 2024 Apr 1;10(4):464-474. doi: 10.1001/jamaoncol.2023.6776.
Hyperbaric Oxygen Therapy and Late Local Toxic Effects in Patients With
Irradiated Breast Cancer: A Randomized Clinical Trial.
Mink van der Molen DR(1), Batenburg MCT(1), Maarse W(2), van den Bongard
DHJG(3), Doeksen A(4), de Lange MY(5), van der Pol CC(6), Evers DJ(7), Lansdorp
CA(8), van der Laan J(1), van de Ven PM(9), van der Leij F(10), Verkooijen
HM(1).
Author information:
(1)Division of Imaging and Oncology, University Medical Centre Utrecht, Cancer
Centre, Utrecht, the Netherlands.
(2)Department of Plastic, Reconstructive and Hand Surgery, University Medical
Centre Utrecht, Utrecht, the Netherlands.
(3)Department of Radiation Oncology, Amsterdam University Medical Centers,
Amsterdam, the Netherlands.
(4)Department of Surgery, St Antonius Hospital, Nieuwegein, the Netherlands.
(5)Alexander Monro Hospital, Bilthoven, the Netherlands.
(6)Department of Surgery, Alrijne Hospital, Leiderdorp, the Netherlands.
(7)Department of Surgery, Hospital Group Twente, Hengelo, the Netherlands.
(8)Da Vinci Clinic, Rotterdam, the Netherlands.
(9)The Julius Center for Health Sciences and Primary Care, Utrecht, the
Netherlands.
(10)Department of Radiation Oncology, University Medical Centre Utrecht, Cancer
Centre, Utrecht, the Netherlands.
Comment on
JAMA Oncol. 2024 Apr 1;10(4):437-438.
IMPORTANCE: Hyperbaric oxygen therapy (HBOT) is proposed as treatment for late
local toxic effects after breast irradiation. Strong evidence of effectiveness
is lacking.
OBJECTIVE: To assess effectiveness of HBOT for late local toxic effects in women
who received adjuvant radiotherapy for breast cancer.
DESIGN, SETTING, AND PARTICIPANTS: This was a hospital-based, pragmatic, 2-arm,
randomized clinical trial nested within the prospective UMBRELLA cohort
following the trials within cohorts design in the Netherlands. Participants
included 189 women with patient-reported moderate or severe breast, chest wall,
and/or shoulder pain in combination with mild, moderate, or severe edema,
fibrosis, or movement restriction 12 months or longer after breast irradiation.
Data analysis was performed from May to September 2023.
INTERVENTION: Receipt of 30 to 40 HBOT sessions over a period of 6 to 8
consecutive weeks.
MAIN OUTCOMES AND MEASURES: Breast, chest wall, and/or shoulder pain 6 months
postrandomization measured by the European Organization for Research and
Treatment of Cancer QLQ-BR23 questionnaire. Secondary end points were
patient-reported fibrosis, edema, movement restriction, and overall quality of
life. Data were analyzed according to intention-to-treat (ITT) and complier
average causal effect (CACE) principles.
RESULTS: Between November 2019 and August 2022, 125 women (median [range] age at
randomization, 56 [37-85] years) with late local toxic effects were offered to
undergo HBOT (intervention arm), and 61 women (median [range] age at
randomization, 60 [36-80] years) were randomized to the control arm. Of those
offered HBOT, 31 (25%) accepted and completed treatment. The most common reason
for not accepting HBOT was high treatment intensity. In ITT, moderate or severe
pain at follow-up was reported by 58 of 115 women (50%) in the intervention arm
and 32 of 52 women (62%) in the control arm (odds ratio [OR], 0.63; 95% CI,
0.32-1.23; P = .18). In CACE, the proportion of women reporting moderate or
severe pain at follow-up was 32% (10 of 31) among those completing HBOT and 75%
(9.7 of 12.9) among control participants expected to complete HBOT if offered
(adjusted OR, 0.34; 95% CI, 0.15-0.80; P = .01). In ITT, moderate or severe
fibrosis was reported by 35 of 107 (33%) in the intervention arm and 25 of 49
(51%) in the control arm (OR, 0.36; 95% CI, 0.15-0.81; P = .02). There were no
significant differences in breast edema, movement restriction, and quality of
life between groups in ITT and CACE.
CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, offering HBOT to
women with late local toxic effects was not effective for reducing pain, but was
effective for reducing fibrosis. In the subgroup of women who completed HBOT, a
significant reduction in pain and fibrosis was observed. A smaller than
anticipated proportion of women with late local toxic effects was prepared to
undergo HBOT.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04193722.
DOI: 10.1001/jamaoncol.2023.6776
PMCID: PMC10853873
PMID: 38329746 [Indexed for MEDLINE]
Conflict of interest statement: Conflict of Interest Disclosures: None reported.
